Studies on the hepatotoxicity of galactosamine/endotoxin or galactosamine/TNF in the perfused mouse liver.
Livers of male albino NMRI mice were perfused in situ at a flow rate of 3 ml/min/g liver in a non-recirculation system. The organs remained intact for at least 3 hr as assessed by release of lactate dehydrogenase (LDH) into the perfusate and by constant O2 consumption. The infusion of the following agents did not cause significant enzyme release or microscopically visible organ injuries: galactosamine (1.8 mg/ml), endotoxin (1 microgram/ml), murine recombinant tumor necrosis factor alpha (0.3 micrograms/ml/g) or combinations of them. In contrast, in vivo pretreatment of the animals with 700 mg/kg galactosamine + 5 micrograms/kg endotoxin, or 700 mg/kg galactosamine + 15 micrograms/kg tumor necrosis factor alpha (TNF) led to a massive LDH release into the perfusate. Infusion of uridine (0.67 mg/ml/g) into perfused livers from animals in vivo pretreated with either galactosamine/endotoxin or galactosamine/TNF, prevented LDH release and histologically visible liver injury. We conclude from these findings that in vivo pretreatment of the animals resulted in latent and reversible damage of the liver induced by extrahepatic factors which are prevented by intrahepatic events sensitive to uridine.
Wang
J F
JF
University of Konstanz, Faculty of Biology, Federal Republic of Germany.
Wendel
A
A
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000378:metabolism; D004731:Endotoxins / Q000008:administration & dosage / Q000633:toxicity*; D005688:Galactosamine / Q000008:administration & dosage* / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D051379:Mice; D010477:Perfusion; D012475:Salmonella; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000633:toxicity*; D014529:Uridine / Q000008:administration & dosage
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; D007770:L-Lactate Dehydrogenase; D014529:Uridine